Received for publication January 18, 2007.
Revised January 23, 2007.
Accepted for publication January 24, 2007.

Constitutive Trafficking- More than just running in circles?(Relates to "An essential role for constitutive endocytosis, but not activity, in the axonal targeting of the CB1 cannabinoid receptor" by McDonald et al.)

Abstract

The CB1 cannabinoid receptors are among the most highly expressed G protein coupled receptors (GPCR) in the brain. Their activation has been associated with wide-ranging behaviors including cognition, pain perception, drug addiction and memory consolidation and they have been pharmaceutically targeted for pain therapies, smoking cessation, and appetite control. The CB1 receptor has been challenging to study at the molecular level given the hydrophobic nature of its lipid-based agonists and difficulties expressing the recombinant cDNA in cellular cultures. Early transfection studies in cell cultures revealed predominately intracellular localization of the CB1 receptor and it was not clear whether this was the 'normal' distribution or whether this was some artifact of the cellular model systems (Roche et al., 1999). However, studies of the endogenously expressed CB1 receptors using specific antibodies have shown that the there is almost always a distinct intracellular, vesicular localization of the CB1 receptor (McIntosh et al., 1998, Pettit, et al., 1998). Confocal microscopy analysis reveals that the intracellular CB1 receptors are localized to vesicles which imply that the receptors are "trafficking" or undergoing a continuous cycle of internalization and membrane relocalization. The manuscript by McDonald et al, in this issue of Molecular Pharmacology addresses whether this constitutive trafficking is related to the activation state of the receptor and whether it plays a role in axonal vs. somatodentritic receptor localization.

Key words: Cannabinoid, Sequestration/Internalization